HCN channels in the hippocampus regulate active coping behavior
| Autor: | Daniel A. Nicholson, Kyle A. Lyman, Hongxin Dong, Daniel W. Fisher, Robert J. Heuermann, Ye Han, Kendall M. Foote, Natividad Ybarra, Linda A. Bean, Dane M. Chetkovich |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Coping (psychology) Dominant negative Mice Transgenic Coping behavior Hippocampus Biochemistry Article Peroxins Fight-or-flight response Mice 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Mild stress Adaptation Psychological Avoidance Learning Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels HCN channel Animals Maze Learning Neurotransmitter Swimming Gene knockdown biology Depression Pyramidal Cells Membrane Proteins Mice Inbred C57BL Disease Models Animal Microscopy Electron 030104 developmental biology chemistry Exploratory Behavior biology.protein Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurochemistry. 146:753-766 |
| ISSN: | 0022-3042 |
| DOI: | 10.1111/jnc.14539 |
| Popis: | Active coping is an adaptive stress response that improves outcomes in medical and neuropsychiatric diseases. To date, most research into coping style has focused on neurotransmitter activity and little is known about the intrinsic excitability of neurons in the associated brain regions that facilitate coping. Previous studies have shown that HCN channels regulate neuronal excitability in pyramidal cells and that HCN channel current (Ih ) in the CA1 area increases with chronic mild stress. Reduction of Ih in the CA1 area leads to antidepressant-like behavior, and this region has been implicated in the regulation of coping style. We hypothesized that the antidepressant-like behavior achieved with CA1 knockdown of Ih is accompanied by increases in active coping. In this report, we found that global loss of TRIP8b, a necessary subunit for proper HCN channel localization in pyramidal cells, led to active coping behavior in numerous assays specific to coping style. We next employed a viral strategy using a dominant negative TRIP8b isoform to alter coping behavior by reducing HCN channel expression. This approach led to a robust reduction in Ih in CA1 pyramidal neurons and an increase in active coping. Together, these results establish that changes in HCN channel function in CA1 influences coping style. |
| Databáze: | OpenAIRE |
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